Sympathetic innervation of the heart plays a critical role in arrhythmogenesis and recent studies have highlighted the role of surgical sympathetic denervation in management of refractory ventricular arrhythmias. The procedure although safe is very invasive and performed via thoracoscopy using single lung ventilation. This is not tolerated by patients with lung disease or severe structural heart disease. Our proposal will validate a completely new minimally invasive method for cardiac sympathetic denervation that can be performed in the interventional labs to replace the current surgical denervation to treat arrhythmic disorders of the heart. Our approach is novel in that we are able to exploit the anatomy of the cardiac nerves to achieve bilateral sympathetic denervation at a single site in front of the tracheal bifurcation. We will also validate an acute assay for denervation that will guide the procedure and ensure success by acute confirmation and safety of the procedure by avoiding unnecessary ablation. This project will be completed in several sequential stages. In Phase I we will demonstrate the proof of concept by demonstrating anesthetic block of the cardiac sympathetic nerves in the pretracheal region and abolishing the cardiac sympathetic response to electrical stimulation of bilateral stellate ganglia. We will show the feasibility and efficacy of RF ablation in the pre-tracheal region in abolishing the stellate sympathetic response and demonstrate acute safety. In Phase II of this proposal we will design and build a stand-alone human grade trans-bronchial ablation device with ultrasound imaging capabilities that will enable easy and safe access to the pretracheal space to achieve ablation of the deep cardiac plexus. We will demonstrate safety and durability of transtracheal RF ablation in a porcine chronic survival model. Sympathetic over activity is uniformly associated with poor survival in all forms of heart disease. Successful completion of the specific aims will lead to development of a novel method and a device to interrupt cardiac sympathetic nerves. Abolishing cardiac response to abnormal neurally mediated sympathetic discharge may have an enormous role in treatment of other cardiac arrhythmias such as atrial fibrillation and cardiac disorders associated with abnormal sympathovagal balance such as heart failure.